Boundary Associated Long Noncoding RNA Mediates Long-Range Chromosomal Interactions.
Boundary Associated Long Noncoding RNA Mediates Long-Range Chromosomal Interactions.
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DOI：
10.1371/journal.pone.0136104
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kim TH
中科院分区：
文献类型：
--
作者：
Nwigwe IJ;Kim YJ;Wacker DA;Kim TH
CCCTC结合因子（CTCF）与其他定义亚染色体结构的因子一起参与将染色体组织成大碱基大小的拓扑相关结构域（TADs）沿着。CTCF-粘附素相互作用已被证明对于转录绝缘活性至关重要，因为它稳定了远程相互作用以促进适当的基因表达。以前的研究表明，CTCF的异染色质边界活动可能是独立的Cohesin，并可能有额外的机制来定义拓扑结构域。在这里，我们表明，边界网站，我们以前确定为CTCF结合位点5（CBS 5）从同源异型基因簇A（HOXA）位点表现出强大的启动子活性。来自CBS 5边界元件的启动子活性产生长非编码RNA，我们将其命名为边界相关长非编码RNA-1（blncRNA 1）。这种RNA的功能表征表明，转录稳定在HOXA基因座的远程相互作用，并促进HOXA基因的正确表达。此外，我们的功能分析还表明，这种RNA在CTCF-粘附素相互作用的稳定中是不需要的，然而CTCF-粘附素相互作用在blncRNA 1的转录中是关键的。因此，CTCF相关的边界元件，CBS 5，采用粘结和非编码RNA建立和维持拓扑相关的结构域在HOXA基因座。
CCCTC binding factor (CTCF) is involved in organizing chromosomes into mega base-sized, topologically associated domains (TADs) along with other factors that define sub-TAD organization. CTCF-Cohesin interactions have been shown to be critical for transcription insulation activity as it stabilizes long-range interactions to promote proper gene expression. Previous studies suggest that heterochromatin boundary activity of CTCF may be independent of Cohesin, and there may be additional mechanisms for defining topological domains. Here, we show that a boundary site we previously identified known as CTCF binding site 5 (CBS5) from the homeotic gene cluster A (HOXA) locus exhibits robust promoter activity. This promoter activity from the CBS5 boundary element generates a long noncoding RNA that we designate as boundary associated long noncoding RNA-1 (blncRNA1). Functional characterization of this RNA suggests that the transcript stabilizes long-range interactions at the HOXA locus and promotes proper expression of HOXA genes. Additionally, our functional analysis also shows that this RNA is not needed in the stabilization of CTCF-Cohesin interactions however CTCF-Cohesin interactions are critical in the transcription of blncRNA1. Thus, the CTCF-associated boundary element, CBS5, employs both Cohesin and noncoding RNA to establish and maintain topologically associated domains at the HOXA locus.